New insights to the many aspects of asthma: “A disease of a thousand faces” Lon Chaney (1883–1930): The Man of a Thousand Faces

Leonidas Frank “Lon” Chaney, American stage and film actor, director, and screenwriter is regarded as one of the most versatile and powerful actors of the early silent film era, renowned for his characterizations of tortured, often grotesque and afflicted characters, and his groundbreaking artistry with makeup. Chaney was one of four children born to deaf parents and, as a result, learned how to communicate with his parents by using his hands and face, expressing a variety of emotions without ever uttering a single word. His ability to transform himself in silent film by using makeup techniques earned him the moniker “The Man of a Thousand Faces.”

True to its name, asthma is “A Disease of a Thousand Faces.” This issue of the Proceedings features a variety of articles that focus on the spectrum of disease expression that relate to asthma and its many faces. The articles summarized herein contain new insights regarding associated risks, phenotypes, control, pathophysiology, biomarkers, and treatment.

A previous study reported by investigators at the Mayo Clinic linked childhood asthma with an increased risk of herpes zoster in adulthood¹ These same investigators more recently reported a waning of protective levels of measles antibody concentrations after measles immunization in children with asthma.² Because it is not known how pervasive these observations might relate to other vaccine-preventable diseases, Umaretiya et al.³ set out to determine whether asthma is associated with an increased risk of pediatric varicella infection. By using a retrospective, population-based, case-control format, they examined cases of breakthrough varicella among children between 2005 and 2011 in Olmsted County, Minnesota. Children with a history of asthma were found to have a higher risk of developing breakthrough varicella compared with those without a history of asthma. Based on this previously unrecognized risk, the authors suggest a two-dose varicella vaccine regimen for children with asthma. This recommendation may have additional wide-ranging implications for other immunizations in children with asthma.

Nowhere is the heterogeneity of asthma better illustrated than in the many phenotypic forms in which the disease is expressed. In seeking to identify and characterize those childhood wheezing phenotypes that may relate to asthma persistence in adolescence, Pité et al.⁴ performed a comprehensive study of pediatric asthma phenotypes. By applying a multidimensional statistical model to a prospective cohort study of 308 children, they observed that preschool-age diagnoses of atopy and rhinitis were independent risk factors for asthma persistence in adolescence.

By probing the all-important role of environmental factors and how they may impact asthma control and quality of life in adult patients with asthma, Hsiao et al.⁵ report the results of a study that used a structural equation modeling analysis. The authors observed that wheeze frequency, allergic response frequency, parental asthma, and asthma control were directly associated with quality of life. They indicate that body mass index, work environment, and wheeze frequency should be considered as independent risk factors when assessing asthma control and quality of life in adult patients with asthma.

With a shifting to a focus on asthma pathophysiology and biomarkers, there is increasing evidence that indicates that periostin may not only be a useful predictive biomarker of Th 2 eosinophilic airway inflammation but also may be linked to the pathogenesis of airway remodeling in asthma.⁶ However, because the association between serum periostin and the magnitude of airway wall thickness remains unclear, Hoshino et al.⁷ examined the relationship between serum periostin and airway geometry in asthma. In studying 26 patients with asthma who were steroid naive and appropriate controls, the authors report results that support the pathogenetic role of periostin as a novel biomarker for both eosinophilic inflammation and airway remodeling.

Increasingly important to the understanding of asthma pathophysiology is an awareness of the role of the human microbiome both as a critical inductive element in immune development and protective immunity but also as an environmental site with deleterious disease-inducing sequelae. In a novel study of the fungal microbiome in the exhaled breath condensate of 47 subjects with asthma, Carpagnano et al.⁸ evaluated the possible correlation of this microbial niche with anthropometric and asthma severity data. The authors report the detection of fungal colonization in the exhaled breath condensate of 70% of the subjects with asthma. Fungal colonization was found to be greater in subjects who were nonatopic, obese, and with severe and uncontrolled asthma.

We transition from asthma pathophysiology to treatment. Advances in inhaler technology have led to the development of a novel albuterol multidose dry powder inhaler with an integrated dose counter; the latter provides a valuable, objective assessment of rescue medication usage.⁹ Given et al.¹⁰ sought to evaluate the functionality, reliability, and accuracy of the albuterol multidose dry powder inhaler integrated dose counter in a real-world clinical setting. They report that the albuterol multidose dry powder inhaler dose counter functioned reliably and accurately, and was well tolerated, with a high degree of patient satisfaction in a real-world setting.

A universally accepted dictum of asthma therapy is that efficacy of treatment must always be counterbalanced by safety, particularly in children. In this regard, Skoner¹¹ reviews old and new published reports concerning inhaled corticosteroid and intranasal corticosteroid safety in children and provides insight on how this information may change the way that inhaled corticosteroid and intranasal corticosteroid are used in children with allergy and asthma. Because of the importance of this finding to parents of children who have asthma and allergic rhinitis, the article by Skoner¹¹ was chosen for this issue's “For the Patient” section. This segment, found in the final pages of the print version of this issue and also available online, consists of a one-page article synopsis written in a readily comprehensible fashion to help patients better understand the clinical implications of the full article.

Systemic corticosteroids have been used in the treatment of asthma since 1950 and remain the mainstay for management of asthma exacerbations and for severe persistent corticosteroid dependent asthma.¹² Klaustermeyer and Choi¹³ provide an updated overview of clinical considerations of systemic corticosteroid use in severe adult asthma.

Aspirin (ASA) desensitization is a therapeutic option in patients with NSAID–exacerbated respiratory disease.¹⁴ However, the mechanism by which desensitization achieves its success in the improvement of symptoms associated with rhinosinusitis and asthma remains unknown. Makowska et al.¹⁵ performed a study that correlated the release of eicosanoid metabolites in urine with the clinical effectiveness of ASA desensitization. They studied eight patients with NSAID–exacerbated respiratory disease who were successfully desensitized and treated with 650 mg of ASA daily for 3 months. The authors found that clinical improvement in rhinosinusitis and asthma after ASA desensitization was not related to changes in urinary eicosanoids metabolites.

External nasal dilator strips improve nasal airflow and provide temporary relief from congestion.¹⁶ Johnson et al.¹⁷ sought to assess and correlate objective and subjective measures of efficacy of two nasal strip variants in children with nasal congestion. They report that both variants worked well to improve objective measurements of nasal air flow.

In an attempt to analyze the utility of available laboratory tests in diagnosing Hymenoptera venom allergy, Vachová et al.¹⁸ studied 95 patients with Hymenoptera venom allergy and with clear histories, and confirmed positive skin test results to bee or wasp venom, and examined serum-specific IgE to venom extracts and available recombinant molecules. In addition, basophil-activation tests with venom extracts were assessed in all the patients. Test sensitivity and specificity were calculated, and receiver operating characteristic and statistical analysis of utility of different combinations of laboratory tests were performed. Based on this extensive analysis, the authors conclude that currently used laboratory tests represent very effective tools for the diagnosis of Hymenoptera venom allergy.

In a concise review of hemophagocytic lymphohistiocytosis, Sifers et al.¹⁹ share clinical pearls related to the diagnosis of this potentially life-threatening disease, which presents the clinical manifestations of hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages.

In this issue's Patient-Oriented Problem Solving “POPS” case presentation, Yamamoto and Khan²⁰ explore the differential diagnosis of dyspnea and chest tightness in a 45-year-old man with obstructive lung disease and eosinophilia. This recurring feature of the Proceedings is traditionally written by an allergy/immunology fellow-in-training from one of the U.S. allergy/immunology training programs. The purpose of the POPS series is to provide an innovative and practical learning experience for the novice allergist/immunologist in training by using a didactic format of clinical presentation and deductive reasoning. The case report demonstrates the complexity of the differential diagnostic process for this clinical presentation and illustrates the importance of a carefully performed history, physical examination, and appropriate laboratory assessment in arriving at the underlying cause of this patient's eosinophilia.

In summary, the collection of articles that illustrate the thousand faces of asthma found within the pages of this issue provides further insight into the important allergic and respiratory disorders that afflict patients whom the allergist/immunologist serves. In keeping with the overall mission of the Proceedings, which is to distribute timely information regarding advancements in the knowledge and practice of allergy, asthma, and immunology to clinicians entrusted with the care of patients, it is our hope that the articles found within this issue will help foster enhanced patient management and outcomes. On behalf of the editorial board, we hope you enjoy the diversity of literature offered in this issue of the Proceedings.